Liu Xiaochun, Mayes Maureen D, Tan Filemon K, Wu Minghua, Reveille John D, Harper Brock E, Draeger Hilda T, Gonzalez Emilio B, Assassi Shervin
University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Arthritis Rheum. 2013 Jan;65(1):226-35. doi: 10.1002/art.37742.
To measure interferon (IFN)-inducible chemokines in the plasma of patients with systemic sclerosis (SSc) and investigate whether the chemokine levels are correlated with disease severity.
Plasma levels of the IFN-inducible chemokines IFNγ-inducible protein 10 (IP-10/CXCL10), IFN-inducible T cell α chemoattractant (I-TAC/CXCL11), and monocyte chemoattractant protein 1 (CCL2) were measured in SSc patients and examined for correlation with the IFN gene expression signature. A composite IFN-inducible chemokine score was generated for chemokines showing a correlation with the IFN gene signature (IP-10 and I-TAC), and this score was compared between 266 patients with SSc enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort and 97 matched control subjects. Subsequently, the correlation between the IFN-inducible chemokine score at baseline and markers of disease severity was assessed. In addition, the course of the IFN-inducible chemokine score over time was examined.
The plasma IFN-inducible chemokine score correlated with the IFN gene expression signature, and this score was higher in SSc patients compared to controls. The IFN-inducible chemokine score was also associated with the absence of anti-RNA polymerase III antibodies and presence of anti-U1 RNP antibodies, but not with disease duration, disease type, or other autoantibodies. The chemokine score correlated with concomitantly obtained scores on the Medsger Severity Index for muscle, skin, and lung involvement in SSc, as well as the forced vital capacity, diffusing capacity for carbon monoxide, and creatine kinase levels. The association of the chemokine score with disease severity was independent of the presence of anti-U1 RNP or other potential confounders (age, sex, ethnicity, disease duration, and treatment with immunosuppressive agents). Finally, there was not a significant change in the IFN-inducible chemokine score over time.
The IFN-inducible chemokine score is a stable serologic marker of a more severe form of SSc and may be useful for risk stratification of patients, regardless of disease type (limited or diffuse) or duration of disease.
检测系统性硬化症（SSc）患者血浆中干扰素（IFN）诱导的趋化因子，并研究趋化因子水平是否与疾病严重程度相关。
检测SSc患者血浆中IFN诱导的趋化因子IFNγ诱导蛋白10（IP-10/CXCL10）、IFN诱导T细胞α趋化因子（I-TAC/CXCL11）和单核细胞趋化蛋白1（CCL2）的水平，并检查其与IFN基因表达特征的相关性。为与IFN基因特征相关的趋化因子（IP-10和I-TAC）生成一个复合IFN诱导趋化因子评分，并在硬皮病结局研究（GENISOS）队列中纳入的266例SSc患者和97例匹配的对照受试者之间比较该评分。随后，评估基线时IFN诱导趋化因子评分与疾病严重程度标志物之间的相关性。此外，还检查了IFN诱导趋化因子评分随时间的变化过程。
血浆IFN诱导趋化因子评分与IFN基因表达特征相关，且SSc患者的该评分高于对照组。IFN诱导趋化因子评分还与抗RNA聚合酶III抗体的缺乏和抗U1 RNP抗体的存在相关，但与疾病持续时间、疾病类型或其他自身抗体无关。趋化因子评分与同时获得的SSc患者肌肉、皮肤和肺部受累的Medsger严重程度指数评分以及用力肺活量、一氧化碳弥散量和肌酸激酶水平相关。趋化因子评分与疾病严重程度的关联独立于抗U1 RNP或其他潜在混杂因素（年龄、性别、种族、疾病持续时间和免疫抑制剂治疗）的存在。最后，IFN诱导趋化因子评分随时间没有显著变化。
IFN诱导趋化因子评分是更严重形式的SSc的一个稳定血清学标志物，可能有助于对患者进行风险分层，而不论疾病类型（局限性或弥漫性）或疾病持续时间如何。
